In vitro transdermal permeation behavior of isosorbide dinitrate in the absence and presence of 2-hydroxypropyl-β-cyclodextrin: solutions and suspensions

• Published in: Journal of inclusion phenomena and macrocyclic chemistry Vol. 96; no. 1-2; pp. 137 - 143
• Main Authors: Zao, Katsutoshi, Ishiguro, Takako, Iohara, Daisuke, Anraku, Makoto, Seo, Hakaru, Irie, Tetsumi, Uekama, Kaneto, Hirayama, Fumitoshi
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-02-2020; Springer Nature B.V
• Subjects: Chemistry; Chemistry and Materials Science; Complexation; Crystallography and Scattering Methods; Cyclodextrins; Dissolution; Food Science; Holes; ISDN; Oleic acid; Organic Chemistry; Original Article; Penetration; Stoichiometry; Isosorbide dinitrate; Cyclodextrin; Skin permeation; Transdermal delivery; Size dependency; Dissolution; Inclusion complex
• ISSN: 1388-3127; 1573-1111
• DOI: 10.1007/s10847-019-00959-x

Interactions of a vasodilator, isosorbide dinitrate (ISDN), with the parent α-, β- and γ-cyclodextrins (α-, β- and γ-CDs) and 2-hydroxypropyl-α- and -β- and γ-CDs (HP-α- and -β- and -γ-CDs) and the dissolution properties of ISDN/β-CD complexes were investigated. The effects of HP-β-CD on the in vitro transdermal permeation of the drug in the forms of solutions and suspensions were also investigated using skin from hairless mice. The size dependent guest–host interactions of CDs were clearly reflected in the stoichiometry of the complexes, i.e. ISDN interacted with two α-CD molecules (which have small cavities) to form a 1:2 (guest:host) complex, while β-CD formed a 1:1 complex. Meanwhile, the large γ-CD cavity included two ISDN molecules to form a 2:1 complex. In the solid state, ISDN was included in a columnar channel formed by the stacking of the parent β-CD, while the HP-β-CD complex was in an amorphous state. The dissolution of ISDN in water increased in the order of the drug alone < the β-CD complex < the HP-β-CD complex. The permeation of ISDN through the skin of hairless mice was significantly decreased in the case of the HP-β-CD, when the drug was in solution. On the other hand, when the drug was in the form of a suspension, the permeation was enhanced by HP-β-CD complexation. The permeation of ISDN in the presence of HP-β-CD in solutions and in suspensions was slightly increased, when oleic acid or linoleic acid were added to the suspension. These results suggest that HP-β-CD complexation has a positive effect on the percutaneous permeation of ISDN when the drug is in the form of a suspension, while the effect is negative when a solution is involved.